Cardiovascular disease, especially atherosclerosis, is the leading cause of death in the United States. One complication often occurring in people with atherosclerosis is the development of abdominal aortic aneurysms (AAA). These aneurysms occur in about 5% of males over the age of 60 and in a lower percentage of females. Risk factors include smoking, a family history of the disease, diabetes and high blood pressure. Atherosclerosis may be treated with medications designed to lower cholesterol levels or blood pressure and with a variety of surgical techniques. Abdominal aneurysms may be treated surgically.
Mast cells (MCs) are recognized as essential effecter cells in the elicitation of the allergic response by releasing cytoplasmic granules, whose contents promote allergic inflammation upon sensitization by IgE or complement factors (Schwartz, et al., Prog. Allergy 34:271-321 (1984); Mekori, et al., J. Allergy Clin. Immunol. 104:517-523 (1999)). Recent biochemical and histological observations suggest that MCs may also participate in blood-borne leukocyte recruitment (Mekori, et al., J. Allergy Clin. Immunol. 104:517-523 (1999)), smooth muscle cell (SMC)/endothelial cell (EC) proliferation (Toda, N., Circ. Res. 61:280-286 (1987); Inoue, et al., Am. J. Pathol. 149:2037-2054 (1996); Mueller, et al., Circ. Res. 77:54-63 (1995)), apoptosis (Latti, et al., J. Cell. Physiol. 195:130-138 (2003); Leskinen, et al., Arterioscler. Thromb. Vasc. Biol. 23:238-2343 (2003); Leskinen, et al., Biochem. Pharmacol. 66:1493-1498 (2003)), T-lymphocyte migration and activation (Mekori, et al., J. Allergy Clin. Immunol. 104:517-23 (1999)), angiogenesis (Zudaire et al., Am. J. Pathol. 168:280-291 (2006)), and matrix remodeling (Daugherty, et al., Curr. Atheroscler. Rep. 4:222-227 (2002)).
A role for MCs in vascular wall remodeling was proposed more than half a century ago and accumulation of MCs correlates with human and murine atherogenesis (Constantinides, Science 117:505-506 (1953); Kovanen, et al., Circulation 92:1084-1088 (1995)). In addition, the appearance of MCs in human cerebral arteries after aneurysm rupture has been reported (Faleiro, et al., J. Neurosurg. 54:733-5 (1981)). If it can be established that MCs are necessary for the development of atherosclerosis or AAA, then methods of treatment and prevention aimed specifically at altering the activity of these cells could be developed. Known methods for the treatment of allergies based upon altering MC function would have the potential of also being useful for cardiovascular disease.